This project explores cellular interactions among T lymphocytes. During this year, the syngeneic mixed leukocyte response was examined by cell number response titrations and limiting dilution analysis to determine the number and nature of the T cells involved inthis apparent autoimmune response. Evidence was obtained for 3 interacting cell populations which recognize and respond by proliferation to Ia molecules on a syngeneic radioresistant 4th stimulating cell population. The particular Ia molecules which are recognized is determined in the thymus during T cell differentiation. One of the T cells is Lyt 1+2-and one or more of the T cells produces T cell growth factor. The frequency of one of the cells is 1/25,000, and the frequence of one other is approximately 10-fold higher. Thus, the syngeneic mixed leukocyte response appears to be a complex series of cellular interactions which could potentially provide a good model for a primary immune response in vitro.